Osteoarthritis (degenerative joint disease) is the most common form of arthritis. It occurs almost universally in the aged and is of significant medical disability in 20% of these cases. The disease is often characterized by articular cartilage degeneration, abnormal cartilage and bone formation (osteochondrophytic spurs) and cystic changes in the subchondral bone. Therapy at the present time is symptomatic rather than specific. Recent advances have indicated that pathogenesis is multifactorial, but at least in part, involves impairment of articular chondrocyte function. Delineation of the etiology of osteoarthritis in man remains difficult because of the relative inability to study the metabolism of the chondrocytes in carefully controlled microenvironments and hence progression of this disease cannot be followed rigorously. Already established cell and tissue culture techniques can now be utilized to delineate metabolic differences in chondrocytes in normal, aged and osteoarthritic human cartilage. The principal objective of this proposal is to determine whether differences exist in the in vitro behavior of articular chondrocytes as a function of the topographical anatomy of normal, aged and osteoarthritic human femoral head and knee cartilage. Further understanding of osteoarthritic processes in human studies will hopefully allow development of specific therapeutic agents to prevent, retard or reverse the disease process.